At least two purine enzyme deficiencies have been associated with immunodeficiency diseases. Adenosine deaminase (ADA) deficiency is associated with severe combined immunodeficiency disease and purine nucleoside phosphorylase (PNPase) deficiency is associated with a loss of cellular immunity. Nucleosides which accumulate in these enzyme deficiencies, i.e., adenosine, deoxyadenosine, and deoxyguanosine, appear to play causal roles in the immune dysfunction. The biochemical basis for the unique sensitivity of lymphocytes (T-cells in particular) to these nucleosides is thought to be due to the presence of certain enzymes (kinases) in lymphocyte subpopulations. These enzymes "salvage" the toxic nucleosides preferentially when compared to other tissues. The biochemical make-up, therefore, of a particular lymphocyte subpopulation can be anticipated to contain relatively high levels of the appropriate kinases. The proposed project will attempt to: 1) identify the T-lymphocyte subsets which are uniquely sensitive to these and other nucleosides; and 2) characterize these subsets immunologically and biochemically. The results obtained with normal and neoplastic T-cell counterparts will be compared to assess changes which may occur with malignant conversion. The long-term objective will be to identify those characteristics of lymphocytes which confer sensitivity to these nucleosides so that a rational approach to treatment of T-cell (and even, B-cell) malignancies can be devised.